Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Aug;94(2):663–671. doi: 10.1172/JCI117383

Stimulation of lung epithelial liquid clearance by endogenous release of catecholamines in septic shock in anesthetized rats.

J F Pittet 1, J P Wiener-Kronish 1, M C McElroy 1, H G Folkesson 1, M A Matthay 1
PMCID: PMC296144  PMID: 8040320

Abstract

Exogenous administration of beta-adrenergic agonists has previously been reported to increase lung liquid clearance by stimulation of active sodium transport across the alveolar epithelium. We hypothesized for this study that endogenous release of epinephrine in septic shock would stimulate liquid clearance from the airspaces in rats. Liquid clearance from the air spaces was measured by the concentration of protein over 4 h in a test solution of 5% albumin instilled into one lung. Bacteremic rats developed severe systemic hypotension and metabolic acidosis that was associated with a 100-fold rise in plasma epinephrine levels. There was a 100% increase in liquid clearance from the airspaces of the lung in the bacteremic compared with control rats. To determine the mechanisms responsible for this accelerated lung liquid clearance, amiloride (10(-3) M), a sodium transport inhibitor, was added to the air spaces. Amiloride prevented the increase in liquid clearance from the airspaces, indicating that this effect depended on increased uptake of sodium across the lung epithelium. The addition of propranolol (10(-4) or 10(-5) M) to the instillate also prevented the acceleration in alveolar liquid clearance in the bacteremic rats. We conclude that the release of endogenous catecholamines associated with septic shock markedly stimulates fluid clearance from the distal airspaces of the lung by a beta-adrenergic mediated stimulation of active sodium transport across the epithelial barrier. This data provides evidence for a previously unrecognized mechanism that can protect against or hasten the resolution of alveolar edema in pathological conditions, such as septic shock, that are associated with the endogenous release of catecholamines.

Full text

PDF
668

Images in this article

666Image
on p.666
667Image
on p.667
667Image
on p.667

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ariëns E. J., Simonis A. M. Physiological and pharmacological aspects of adrenergic receptor classification. Biochem Pharmacol. 1983 May 15;32(10):1539–1545. doi: 10.1016/0006-2952(83)90324-6. [DOI] [PubMed] [Google Scholar]
  2. Basset G., Crone C., Saumon G. Fluid absorption by rat lung in situ: pathways for sodium entry in the luminal membrane of alveolar epithelium. J Physiol. 1987 Mar;384:325–345. doi: 10.1113/jphysiol.1987.sp016457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Basset G., Crone C., Saumon G. Significance of active ion transport in transalveolar water absorption: a study on isolated rat lung. J Physiol. 1987 Mar;384:311–324. doi: 10.1113/jphysiol.1987.sp016456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baue A. E., Günther B., Hartl W., Ackenheil M., Heberer G. Altered hormonal activity in severely ill patients after injury or sepsis. Arch Surg. 1984 Oct;119(10):1125–1132. doi: 10.1001/archsurg.1984.01390220011003. [DOI] [PubMed] [Google Scholar]
  5. Berthiaume Y., Albertine K. H., Grady M., Fick G., Matthay M. A. Protein clearance from the air spaces and lungs of unanesthetized sheep over 144 h. J Appl Physiol (1985) 1989 Nov;67(5):1887–1897. doi: 10.1152/jappl.1989.67.5.1887. [DOI] [PubMed] [Google Scholar]
  6. Berthiaume Y., Broaddus V. C., Gropper M. A., Tanita T., Matthay M. A. Alveolar liquid and protein clearance from normal dog lungs. J Appl Physiol (1985) 1988 Aug;65(2):585–593. doi: 10.1152/jappl.1988.65.2.585. [DOI] [PubMed] [Google Scholar]
  7. Berthiaume Y., Staub N. C., Matthay M. A. Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep. J Clin Invest. 1987 Feb;79(2):335–343. doi: 10.1172/JCI112817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brigham K. L., Woolverton W. C., Blake L. H., Staub N. C. Increased sheep lung vascular permeability caused by pseudomonas bacteremia. J Clin Invest. 1974 Oct;54(4):792–804. doi: 10.1172/JCI107819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brown M. J., Olver R. E., Ramsden C. A., Strang L. B., Walters D. V. Effects of adrenaline and of spontaneous labour on the secretion and absorption of lung liquid in the fetal lamb. J Physiol. 1983 Nov;344:137–152. doi: 10.1113/jphysiol.1983.sp014929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Carstairs J. R., Nimmo A. J., Barnes P. J. Autoradiographic visualization of beta-adrenoceptor subtypes in human lung. Am Rev Respir Dis. 1985 Sep;132(3):541–547. doi: 10.1164/arrd.1985.132.3.541. [DOI] [PubMed] [Google Scholar]
  11. Casale T. B., Wood D., Wescott S., Kaliner M. Immunohistochemical identification of lung cells responsive to beta-stimulation with a rise in cAMP. J Appl Physiol (1985) 1987 Jul;63(1):434–439. doi: 10.1152/jappl.1987.63.1.434. [DOI] [PubMed] [Google Scholar]
  12. Chapman D. L., Carlton D. P., Nielson D. W., Cummings J. J., Poulain F. R., Bland R. D. Changes in lung lipid during spontaneous labor in fetal sheep. J Appl Physiol (1985) 1994 Feb;76(2):523–530. doi: 10.1152/jappl.1994.76.2.523. [DOI] [PubMed] [Google Scholar]
  13. Cott G. R., Sugahara K., Mason R. J. Stimulation of net active ion transport across alveolar type II cell monolayers. Am J Physiol. 1986 Feb;250(2 Pt 1):C222–C227. doi: 10.1152/ajpcell.1986.250.2.C222. [DOI] [PubMed] [Google Scholar]
  14. Crandall E. D., Heming T. A., Palombo R. L., Goodman B. E. Effects of terbutaline on sodium transport in isolated perfused rat lung. J Appl Physiol (1985) 1986 Jan;60(1):289–294. doi: 10.1152/jappl.1986.60.1.289. [DOI] [PubMed] [Google Scholar]
  15. DeBlasi A., Maisel A. S., Feldman R. D., Ziegler M. G., Fratelli M., DiLallo M., Smith D. A., Lai C. Y., Motulsky H. J. In vivo regulation of beta-adrenergic receptors on human mononuclear leukocytes: assessment of receptor number, location, and function after posture change, exercise, and isoproterenol infusion. J Clin Endocrinol Metab. 1986 Oct;63(4):847–853. doi: 10.1210/jcem-63-4-847. [DOI] [PubMed] [Google Scholar]
  16. Effros R. M., Mason G. R., Hukkanen J., Silverman P. New evidence for active sodium transport from fluid-filled rat lungs. J Appl Physiol (1985) 1989 Feb;66(2):906–919. doi: 10.1152/jappl.1989.66.2.906. [DOI] [PubMed] [Google Scholar]
  17. Effros R. M., Mason G. R., Hukkanen J., Silverman P. Reabsorption of solutes and water from fluid-filled rabbit lungs. Am Rev Respir Dis. 1987 Sep;136(3):669–676. doi: 10.1164/ajrccm/136.3.669. [DOI] [PubMed] [Google Scholar]
  18. Ekelund L., Burgoyne R., Enhorning G. Pulmonary surfactant release in fetal rabbits: immediate and delayed response to terbutaline. Am J Obstet Gynecol. 1983 Oct 15;147(4):437–443. doi: 10.1016/s0002-9378(16)32240-2. [DOI] [PubMed] [Google Scholar]
  19. Fabisiak J. P., Vesell E. S., Rannels D. E. Interactions of beta adrenergic antagonists with isolated rat alveolar type II pneumocytes. I. Analysis, characterization and regulation of specific beta adrenergic receptors. J Pharmacol Exp Ther. 1987 May;241(2):722–727. [PubMed] [Google Scholar]
  20. Fitzgerald J. D., Wale J. L., Austin M. The haemodynamic effects of ( )-propranolol, dexpropranolol, oxprenolol, practolol and sotalol in anaesthetised dogs. Eur J Pharmacol. 1972 Jan;17(1):123–134. doi: 10.1016/0014-2999(72)90278-6. [DOI] [PubMed] [Google Scholar]
  21. Garty H., Benos D. J. Characteristics and regulatory mechanisms of the amiloride-blockable Na+ channel. Physiol Rev. 1988 Apr;68(2):309–373. doi: 10.1152/physrev.1988.68.2.309. [DOI] [PubMed] [Google Scholar]
  22. Goodman B. E., Brown S. E., Crandall E. D. Regulation of transport across pulmonary alveolar epithelial cell monolayers. J Appl Physiol Respir Environ Exerc Physiol. 1984 Sep;57(3):703–710. doi: 10.1152/jappl.1984.57.3.703. [DOI] [PubMed] [Google Scholar]
  23. Goodman B. E., Kim K. J., Crandall E. D. Evidence for active sodium transport across alveolar epithelium of isolated rat lung. J Appl Physiol (1985) 1987 Jun;62(6):2460–2466. doi: 10.1152/jappl.1987.62.6.2460. [DOI] [PubMed] [Google Scholar]
  24. Holloway B. W., Krishnapillai V., Morgan A. F. Chromosomal genetics of Pseudomonas. Microbiol Rev. 1979 Mar;43(1):73–102. doi: 10.1128/mr.43.1.73-102.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Holter J. F., Weiland J. E., Pacht E. R., Gadek J. E., Davis W. B. Protein permeability in the adult respiratory distress syndrome. Loss of size selectivity of the alveolar epithelium. J Clin Invest. 1986 Dec;78(6):1513–1522. doi: 10.1172/JCI112743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jayr C., Garat C., Meignan M., Pittet J. F., Zelter M., Matthay M. A. Alveolar liquid and protein clearance in anesthetized ventilated rats. J Appl Physiol (1985) 1994 Jun;76(6):2636–2642. doi: 10.1152/jappl.1994.76.6.2636. [DOI] [PubMed] [Google Scholar]
  27. Jayr C., Matthay M. A. Alveolar and lung liquid clearance in the absence of pulmonary blood flow in sheep. J Appl Physiol (1985) 1991 Nov;71(5):1679–1687. doi: 10.1152/jappl.1991.71.5.1679. [DOI] [PubMed] [Google Scholar]
  28. Liggett S. B., Marker J. C., Shah S. D., Roper C. L., Cryer P. E. Direct relationship between mononuclear leukocyte and lung beta-adrenergic receptors and apparent reciprocal regulation of extravascular, but not intravascular, alpha- and beta-adrenergic receptors by the sympathochromaffin system in humans. J Clin Invest. 1988 Jul;82(1):48–56. doi: 10.1172/JCI113600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mason R. J., Williams M. C., Widdicombe J. H., Sanders M. J., Misfeldt D. S., Berry L. C., Jr Transepithelial transport by pulmonary alveolar type II cells in primary culture. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6033–6037. doi: 10.1073/pnas.79.19.6033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Matalon S. Mechanisms and regulation of ion transport in adult mammalian alveolar type II pneumocytes. Am J Physiol. 1991 Nov;261(5 Pt 1):C727–C738. doi: 10.1152/ajpcell.1991.261.5.C727. [DOI] [PubMed] [Google Scholar]
  31. Matthay M. A., Berthiaume Y., Staub N. C. Long-term clearance of liquid and protein from the lungs of unanesthetized sheep. J Appl Physiol (1985) 1985 Sep;59(3):928–934. doi: 10.1152/jappl.1985.59.3.928. [DOI] [PubMed] [Google Scholar]
  32. Matthay M. A., Landolt C. C., Staub N. C. Differential liquid and protein clearance from the alveoli of anesthetized sheep. J Appl Physiol Respir Environ Exerc Physiol. 1982 Jul;53(1):96–104. doi: 10.1152/jappl.1982.53.1.96. [DOI] [PubMed] [Google Scholar]
  33. Matthay M. A., Wiener-Kronish J. P. Intact epithelial barrier function is critical for the resolution of alveolar edema in humans. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1250–1257. doi: 10.1164/ajrccm/142.6_Pt_1.1250. [DOI] [PubMed] [Google Scholar]
  34. McDonald J. V., Jr, Gonzales L. W., Ballard P. L., Pitha J., Roberts J. M. Lung beta-adrenoreceptor blockade affects perinatal surfactant release but not lung water. J Appl Physiol (1985) 1986 May;60(5):1727–1733. doi: 10.1152/jappl.1986.60.5.1727. [DOI] [PubMed] [Google Scholar]
  35. Nelson R. M., McIntyre B. R., Egan E. A. Solute permeability of the alveolar epithelium in alloxan edema in dogs. J Appl Physiol Respir Environ Exerc Physiol. 1978 Mar;44(3):353–357. doi: 10.1152/jappl.1978.44.3.353. [DOI] [PubMed] [Google Scholar]
  36. O'Brodovich H. Epithelial ion transport in the fetal and perinatal lung. Am J Physiol. 1991 Oct;261(4 Pt 1):C555–C564. doi: 10.1152/ajpcell.1991.261.4.C555. [DOI] [PubMed] [Google Scholar]
  37. Olver R. E., Ramsden C. A., Strang L. B., Walters D. V. The role of amiloride-blockable sodium transport in adrenaline-induced lung liquid reabsorption in the fetal lamb. J Physiol. 1986 Jul;376:321–340. doi: 10.1113/jphysiol.1986.sp016156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Padbury J. F., Hobel C. J., Lam R. W., Fisher D. A. Sex differences in lung and adrenal neurosympathetic development in rabbits. Am J Obstet Gynecol. 1981 Sep 15;141(2):199–204. doi: 10.1016/s0002-9378(16)32593-5. [DOI] [PubMed] [Google Scholar]
  39. Rubin D. B., Wiener-Kronish J. P., Murray J. F., Green D. R., Turner J., Luce J. M., Montgomery A. B., Marks J. D., Matthay M. A. Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome. J Clin Invest. 1990 Aug;86(2):474–480. doi: 10.1172/JCI114733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sakuma T., Pittet J. F., Jayr C., Matthay M. A. Alveolar liquid and protein clearance in the absence of blood flow or ventilation in sheep. J Appl Physiol (1985) 1993 Jan;74(1):176–185. doi: 10.1152/jappl.1993.74.1.176. [DOI] [PubMed] [Google Scholar]
  41. Sano K., Cott G. R., Voelker D. R., Mason R. J. The Na+/H+ antiporter in rat alveolar type II cells and its role in stimulated surfactant secretion. Biochim Biophys Acta. 1988 Apr 22;939(3):449–458. doi: 10.1016/0005-2736(88)90091-0. [DOI] [PubMed] [Google Scholar]
  42. Saumon G., Basset G., Bouchonnet F., Crone C. cAMP and beta-adrenergic stimulation of rat alveolar epithelium. Effects on fluid absorption and paracellular permeability. Pflugers Arch. 1987 Nov;410(4-5):464–470. doi: 10.1007/BF00586526. [DOI] [PubMed] [Google Scholar]
  43. Saumon G., Basset G. Electrolyte and fluid transport across the mature alveolar epithelium. J Appl Physiol (1985) 1993 Jan;74(1):1–15. doi: 10.1152/jappl.1993.74.1.1. [DOI] [PubMed] [Google Scholar]
  44. Schell D. N., Durham D., Murphree S. S., Muntz K. H., Shaul P. W. Ontogeny of beta-adrenergic receptors in pulmonary arterial smooth muscle, bronchial smooth muscle, and alveolar lining cells in the rat. Am J Respir Cell Mol Biol. 1992 Sep;7(3):317–324. doi: 10.1165/ajrcmb/7.3.317. [DOI] [PubMed] [Google Scholar]
  45. Selinger S. L., Bland R. D., Demling R. H., Staub N. C. Distribution volumes of [131I]albumin, [14C]sucrose, and 36Cl in sheep lung. J Appl Physiol. 1975 Nov;39(5):773–779. doi: 10.1152/jappl.1975.39.5.773. [DOI] [PubMed] [Google Scholar]
  46. Sibley D. R., Lefkowitz R. J. Molecular mechanisms of receptor desensitization using the beta-adrenergic receptor-coupled adenylate cyclase system as a model. Nature. 1985 Sep 12;317(6033):124–129. doi: 10.1038/317124a0. [DOI] [PubMed] [Google Scholar]
  47. Smedira N., Gates L., Hastings R., Jayr C., Sakuma T., Pittet J. F., Matthay M. A. Alveolar and lung liquid clearance in anesthetized rabbits. J Appl Physiol (1985) 1991 Apr;70(4):1827–1835. doi: 10.1152/jappl.1991.70.4.1827. [DOI] [PubMed] [Google Scholar]
  48. Wiener-Kronish J. P., Albertine K. H., Matthay M. A. Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin. J Clin Invest. 1991 Sep;88(3):864–875. doi: 10.1172/JCI115388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wiener-Kronish J. P., Sakuma T., Kudoh I., Pittet J. F., Frank D., Dobbs L., Vasil M. L., Matthay M. A. Alveolar epithelial injury and pleural empyema in acute P. aeruginosa pneumonia in anesthetized rabbits. J Appl Physiol (1985) 1993 Oct;75(4):1661–1669. doi: 10.1152/jappl.1993.75.4.1661. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES